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Pluronic Micelle-Mediated Tissue Factor Silencing Enhances Hemocompatibility, Stemness, Differentiation Potential, and Paracrine Signaling of Mesenchymal Stem Cells
Biomacromolecules. 2021 Apr 5. doi: 10.1021/acs.biomac.1c00070. Online ahead of print.ABSTRACTMesenchymal stem/stromal cells (MSCs) evoke great excitement for treating different human diseases due to their ability to home inflamed tissues, suppress inflammation, and promote tissue regeneration. Despite great promises, clinical trial results are disappointing as allotransplantation of MSCs trigger thrombotic activity and are damaged by the complement system, compromising their survival and function. To overcome this, a new strategy is presented by the silencing of tissue factor (TF), a transmembrane protein that mediates pr...
Source: Biomacromolecules - April 5, 2021 Category: Biochemistry Authors: Vignesh K Rangasami Ganesh Nawale Kenta Asawa Sandeep Kadekar Sumanta Samanta Bo Nilsson Kristina N Ekdahl Susanna Miettinen J öns Hilborn Yuji Teramura Oommen P Varghese Oommen P Oommen Source Type: research

Systemic Delivery of NAC-1 siRNA by Neuropilin-Targeted Polymersomes Sensitizes Antiangiogenic Therapy of Metastatic Triple-Negative Breast Cancer.
Abstract Antiangiogenic therapy with bevacizumab while being interesting for metastatic triple-negative breast cancer (mTNBC) is restrained by tumor hypoxia elevation and cancer stem cell enrichment. Here, we find that neuropilin-1 (NRP-1)-targeted delivery of nucleus accumbens-associated protein-1 (NAC-1) siRNA mediated by tLyP-1 peptide-functionalized chimaeric polymersomes (tLyP-1-Ps) effectively sensitizes antiangiogenic therapy of mTNBC in vivo. tLyP-1-Ps showed good encapsulation (up to 14.4 wt. %) of siNAC-1, giving robust tLyP-1-Ps-siNAC-1 nanoformulation with a defined size of 48.5 nm (PDI = 0.13) and a s...
Source: Biomacromolecules - November 11, 2020 Category: Biochemistry Authors: Wang H, Wang X, Zhang Y, Cheng R, Yuan J, Zhong Z Tags: Biomacromolecules Source Type: research

Insights into siRNA transfection in suspension: Efficient gene silencing in human mesenchymal stem cells encapsulated in hyaluronic acid hydrogel.
Abstract Small interfering RNAs (siRNAs) are powerful tools for post-transcriptional gene silencing which offers enormous opportunities for tissue engineering applications. However, poor serum stability, inefficient intracellular delivery, and inevitable toxicity of transfection reagents are the key barriers for their clinical translation. Thus innovative strategies that allow safe and efficient intracellular delivery of the nucleic acid drugs at the desired site is urgently needed for a smooth clinical translation of therapeutically appealing siRNA-based technology. In this regard, we have developed an innovative...
Source: Biomacromolecules - January 14, 2019 Category: Biochemistry Authors: Paidikondala M, Nawale GN, Varghese OP Tags: Biomacromolecules Source Type: research

Diblock copolymer hydrophobicity facilitates efficient gene silencing and cytocompatible nanoparticle-mediated siRNA delivery to musculoskeletal cell types.
Abstract pH-responsive diblock copolymers provide tailorable nanoparticle (NP) architecture and chemistry critical for siRNA delivery. Here, diblock polymers varying in first (corona) and second (core) block molecular weight (Mn), Corona:Core ratio and core hydrophobicity (%BMA) were synthesized to determine their effect on siRNA delivery in murine tenocytes (mTenocyte) and murine and human mesenchymal stem cells (mMSC and hMSCs, respectively). NP-mediated siRNA uptake, gene silencing, and cytocompatibility were quantified. Uptake is positively correlated with first block Mn in mTenocytes and hMSCs (p≤0.0005). A...
Source: Biomacromolecules - September 29, 2017 Category: Biochemistry Authors: Malcolm DW, Freeberg MAT, Wang Y, Sims KR, Awad HA, Benoit DSW Tags: Biomacromolecules Source Type: research

EpCAM-Antibody-Labeled Noncytotoxic Polymer Vesicles for Cancer Stem Cells-Targeted Delivery of Anticancer Drug and siRNA.
Abstract Cancer stem cells (CSCs) have the capability to initiate tumor, to sustain tumor growth, to maintain the heterogeneity of tumor, and are closely linked to the failure of chemotherapy due to their self-renewal and multilineage differentiation capability with an innate resistance to cytotoxic agents. Herein, we designed and synthesized a novel anti-EpCAM (epithelial cell adhesion molecule)-monoclonal-antibody-labeled CSCs-targeting, noncytotoxic and pH-sensitive block copolymer vesicle as a nano-carrier of anticancer drug and siRNA (to overcome CSCs drug resistance by silencing the expression of oncogenes)....
Source: Biomacromolecules - May 19, 2015 Category: Biochemistry Authors: Chen J, Liu Q, Xiao J, Du J Tags: Biomacromolecules Source Type: research

Smurf1 knocked-down, mesenchymal stem cells and BMP-2 in an electrospun system for bone regeneration.
Abstract A sandwich-like system, fabricated with electrospun, poly (lactic-co-glycolic-acid) (PLGA) membranes incorporating either human recombinant bone morphogenetic protein 2 (BMP-2) enriched microspheres, rat bone marrow mesenchymal stem cells (rMSC), or rMSC with their Smurf1 (Smad Ubiquitin Regulatory Factor-1) expression knocked down by means of siRNA (rMSC573) at varying densities was evaluated in a rat calvarial, critical-size defect. The behavior of four membrane varieties, fabricated with different PLGA copolymers, was initially studied in rMSC cultures to decide on optimal membrane degradation and cell...
Source: Biomacromolecules - February 22, 2014 Category: Biochemistry Authors: Rodriguez-Evora M, García-Pizarro E, Del Rosario C, Perez-Lopez J, Reyes R, Delgado A, Rodriguez-Rey JC, Evora C Tags: Biomacromolecules Source Type: research